title: Killer immunoglobulin-like receptor and human leukocyte antigen-C genotypes in rheumatoid arthritis primary responders and non-responders to anti-TNF-α therapy.
abstract: The identification of patients who will respond to anti-tumor necrosis factor alpha (anti-TNF-α) therapy will improve the efficacy, safety, and economic impact of these agents. We investigated whether killer cell immunoglobulin-like receptor (KIR) genes are related to response to anti-TNF-α therapy in patients with rheumatoid arthritis (RA). Sixty-four RA patients and 100 healthy controls were genotyped for 16 KIR genes and human leukocyte antigen-C (HLA-C) group 1/2 using polymerase chain reaction sequence-specific oligonucleotide probes (PCR-SSOP). Each patient received anti-TNF-α therapy (adalimumab, etanercept, or infliximab), and clinical responses were evaluated after 3 months using the disease activity score in 28 joints (DAS28). We investigated the correlations between the carriership of KIR genes, HLA-C group 1/2 genes, and clinical data with response to therapy. Patients responding to therapy showed a significantly higher frequency of KIR2DS2/KIR2DL2 (67.7% R vs. 33.3% NR; P = 0.012). A positive clinical outcome was associated with an activating KIR-HLA genotype; KIR2DS2                         (+)                         HLA-C group 1/2 homozygous. Inversely, non-response was associated with the relatively inhibitory KIR2DS2                         (-)                         HLA-C group 1/2 heterozygous genotype. The KIR and HLA-C genotype of an RA patient may provide predictive information for response to anti-TNF-α therapy.
authors.affiliation: Biomedical Sciences Research Institute, University of Ulster at Coleraine, Cromore Road, Northern Ireland, UK. cathymcgeough@hotmail.co.uk
authors.forename: Cathy M
authors.initials: CM
authors.lastname: McGeough
authors.forename: Daniel
authors.initials: D
authors.lastname: Berrar
authors.forename: Gary
authors.initials: G
authors.lastname: Wright
authors.forename: Clare
authors.initials: C
authors.lastname: Mathews
authors.forename: Paula
authors.initials: P
authors.lastname: Gilmore
authors.forename: Rodat T
authors.initials: RT
authors.lastname: Cunningham
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bjourson
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D000068800:Etanercept; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland; D018579:Patient Selection; D010597:Pharmacogenetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D057285:Precision Medicine; D054340:Receptors, KIR / Q000235:genetics*; D054343:Receptors, KIR2DL2 / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015236:HLA-C Antigens; D007074:Immunoglobulin G; C515077:KIR2DL2 protein, human; C433932:KIR2DS2 protein, human; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept